Pei-Ning Wang

Diffusion Tensor Tractography Reveals Abnormal Topological Organization in Structural Cortical Networks in Alzheimer's Disease

Recent research on Alzheimers disease (AD) has shown that the decline of cognitive and memory functions is accompanied by a disrupted neuronal connectivity characterized by white matter (WM) degeneration. However, changes in the topological organization of WM structural network in AD remain largely unknown. Here, we used diffusion tensor image tractography to construct the human brain WM networks of 25 AD patients and 30 age- and sex-matched healthy controls, followed by a graph theoretical analysis. We found that both AD patients and controls had a small-world topology in WM network, suggesting an optimal balance between structurally segregated and integrative organization. More important, the AD patients exhibited increased shortest path length and decreased global efficiency in WM network compared with controls, implying abnormal topological organization. Furthermore, we showed that the WM network contained highly connected hub regions that were predominately located in the precuneus, cingulate cortex, and dorsolateral prefrontal cortex, which was consistent with the previous diffusion-MRI studies. Specifically, AD patients were found to have reduced nodal efficiency predominantly located in the frontal regions. Finally, we showed that the alterations of various network properties were significantly correlated with the behavior performances. Together, the present study demonstrated for the first time that the Alzheimers brain was associated with disrupted topological organization in the large-scale WM structural networks, thus providing the structural evidence for abnormalities of systematic integrity in this disease. This work could also have implications for understanding how the abnormalities of structural connectivity in AD underlie behavioral deficits in the patients.

Swallowing difficulty in Parkinson's disease

Dysphagia is a frequent and potentially serious complication of Parkinsons disease (PD). We examined the oropharyngeal swallowing ability in 19 PD patients (15 men and 4 women, mean age 68.42 years, mean Hoehn and Yahr stage 1.8) using modified barium swallow before and after administering oral levodopa (in combination with benserazide). Twelve (63.2%) patients demonstrated objective evidence of swallowing abnormalities; although only six patients (31.6%) had subjective complaints. Vallecula sinus and pyriform sinus residues were the most frequent abnormalities (47.4% and 42.1%); followed by delayed swallowing reflex (26.3%). Three patients demonstrated silent aspiration. In the 12 patients with abnormal swallowing, six (50%) showed objective improvement after levodopa treatment, while the remaining six showed no change. Of the former group of six, one patient showed improvement in the oral phase, but deterioration in the pharyngeal phase. We concluded that PD patients had a high percentage of objective swallowing abnormalities which could be reduced in half of the patients through the administration of levodopa treatment.

Weight loss, nutritional status and physical activity in patients with Alzheimer’s Disease

Abstract.The etiology of weight loss in Alzheimer’s disease (AD) patients is still uncertain. This study was designed to investigate the possible factors that might contribute to weight change of AD patients. From July 1999 to June 2001, we recruited 51 AD patients and 27 non-demented controls. Demographic data, neuropsychological tests, Geriatric Depression Scale-Short Form, eating behavior questionnaire, dietary and physical activity diaries, anthropometric and laboratory measures of nutritional status were assessed. More than half of our AD patients developed body weight loss, and overall, the AD patients were significantly thinner than the non-demented subjects. Anthropometric and laboratory measures suggested a poorer nutritional status in the AD patients. The AD patients had fewer daily physical activities. More AD patients had the problem of poor appetite. However, daily calorie intake was not significantly different between the two groups. The AD patients, especially those who presented with body weight loss, even consumed more calories per body weight kilogram (kg) per day. In the food composition analysis, AD patients took more carbohydrate than controls. Multivariate regression analysis showed the existence of AD and poor appetite were the main risk factors of weight loss. We suggest that the pathophysiological process in AD gives rise to the changes of appetite and metabolic state in AD patients, and that these changes contribute to the weight loss.

Cutoff Scores of the Cognitive Abilities Screening Instrument, Chinese Version in Screening of Dementia

The purpose of this study of dementia screening was to obtain different cutoff scores of the Cognitive Abilities Screening Instrument, Chinese versions (CASI C-2.0) for subjects with different educational backgrounds. The diagnosis of dementia was based on the Diagnostic and Statistical Manual of Mental Disorders, ed 3 revised or ed 4 criteria. To diagnose Alzheimer’s disease, the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association was followed. The severity of dementia was determined on the Clinical Dementia Rating scale. Altogether 2,096 subjects, aged 65 years and more, were included. Of them, 1,178 were normal and 918 were demented. Their performance on CASI C-2.0 was influenced by their education and age. Gender difference on CASI C-2.0 scores was only significant in the illiterate, but not in the literate group. We recommend that the population be divided into three levels, namely those who (1) had no formal education (Edu = 0); (2) received 1–5 years of schooling (Edu = 1–5), and (3) received 6 or more years of education (Edu ≧6). The cutoff scores of CASI C-2.0 in the diagnosis of dementia in these three educational groups were as follows: Edu = 0: 49/50 (sensitivity = 0.83; specificity = 0.85); Edu = 1–5: 67/68 (sensitivity = 0.83; specificity = 0.91), and Edu ≧6: 79/80 (sensitivity = 0.89; specificity = 0.90).

Subjective Memory Complaint in Relation to Cognitive Performance and Depression: A Longitudinal Study of a Rural Chinese Population

OBJECTIVES: To examine the associations of subjective memory complaint (SMC) in old age with (a) objective test performance, (b) past and subsequent cognitive decline, and (c) depression.

Prevalence and subtypes of dementia in a rural Chinese population.

We conducted a single-stage community-based study of dementia on all registered residents ≥65 years in age in a rural Chinese community. Neurologists conducted semistructured interviews and examined all participants; they also interviewed family members in cases where dementia was suspected. The diagnosis was made by consensus according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders. 3rd ed, revised (DSM-III-R). Among the 2,055 contacted individuals, 1,736 (84.5%) participated in the study and 44 (13 men and 31 women) were diagnosed as having dementia, including 35 (80%) with probable Alzheimer disease (AD) and 3 (7%) with vascular dementia (VsD). The rates of dementia were 0.5% for ages 65–74 years, 2.9% for ages 75–84 years, and 12.0% for ages 85–101 years. The overall rate was 2.5% for age 65 years. After controlling for age, neither a lack of formal education nor being a woman was a risk factor for dementia. At 2-year follow-up, 30 of the 44 demented participants had died, yielding a 2-year survival rate of 32%. The present results corroborated our previous findings of lower prevalence rates of dementia among the Chinese than among Western populations, and both genetic and sociocultural factors may have contributed to the low rates. The lack of neuroradiological imaging studies in the present study may have contributed to the finding of an unusually low rate of VsD.

Prediction of Alzheimer's disease in mild cognitive impairment: A prospective study in Taiwan

The relationship between apolipoprotein E (ApoE) and clinical manifestations of mild cognitive impairment (MCI) has not been investigated in non-Caucasian populations. This prospective study was conducted in an ethnic Chinese population to evaluate the correlations of ApoE genotype, cognitive performance, medial temporal structure volumes, and clinical outcome in amnestic MCI. Twenty normal elders, 58 MCI, and 20 mild Alzheimers disease (AD) patients received neuropsychological, MRI, and ApoE genotype assessments at baseline. Patients with MCI had intermediate cognitive performance and hippocampal volumes between those in normal and AD groups. In each diagnostic group, epsilon4 carriers (E4+) consistently had smaller hippocampal volume than non-carriers (E4-) did. Nineteen MCI subjects (32.7%) converted to AD during the 3-year study period. Compared with MCI non-converters and E4- MCI converters, E4+ MCI converters had the smallest hippocampal volume. However, epsilon4 was not a predictor for AD. Both cognitive performance and hippocampal volume were predictive for progression to AD. However, stepwise Cox regression model integrating both neuropsychological and radiological variables showed that global cognitive performance was the only significant predictor for AD. A poor global cognitive score may be more crucial than a small hippocampal volume in the prediction of AD.

Comorbidity of headaches and depression in the elderly.

The comorbidity of headache and depression is rarely studied in the elderly. Confounders were seldom controlled in previous studies. From August 1993 to March 1994, we conducted a door-to-door survey to investigate the relationship of headache and depression in a Chinese elderly population (age > or = 65 years old) in two townships of Kinmen, Taiwan. A total of 1421 participants (71%) out of 2003 eligible citizens completed five measurements: a structured headache interview, Geriatric Depression Scale-short form (GDS-S), a survey of chronic medical illness. Cognitive Abilities Screening Instrument and an evaluation of activities of daily living. Headache diagnoses were made according to the criteria of the International Headache Society (IHS), 1988. Depression was defined as a GDS-S score > or = 8. After adjustment for confounding, subjects with more frequent headaches, more severe headaches, diagnoses of IHS migraine or chronic tension-type headaches in the past year, or a lifetime history of any headache including migraine were more likely to be depressed. In addition, the most relevant headache-related predictors of depression were the presence of any reported lifetime headache (odds ratio (OR) = 1.8, P < 0.01) and headache frequency > or = 7 days/month in the past year (OR = 2.0, P = 0.01). This study provided evidence that headache is independently associated with depression in the elderly. A high comorbidity of depression was found in the elderly with IHS migraine or chronic tension-type headaches. Not only the headache profile in the past year but also that in their lifetime was important in predicting current depression in the elderly. 1

Ossification of the posterior longitudinal ligament of the spine. A case-control risk factor study.

STUDY DESIGN A case-control study. OBJECTIVES To determine the risk factors for ossification of the posterior longitudinal ligament (OPLL) of the spine. SUMMARY OF BACKGROUND DATA Previous epidemiologic studies conducted in Japan showed consuming vegetable protein and salt was a risk factor for OPLL. Dietary habits of the Taiwanese and Japanese people are similar. Whether the similar dietary habits play an important role in the high prevalence of OPLL in Taiwan was of interest. METHODS A case-control study was conducted in a tertiary teaching hospital. The study included 98 consecutive cervical spine patients with OPLL, with 98 age-matched patients with cervical spondylosis serving as control subjects. Radiologic examinations, clinical interviews, physical examinations, and risk factor questionnaires were administered to all the participants. RESULTS Compared with incidence in the control patients, the frequency of the ossification of the anterior longitudinal ligaments was significantly higher in OPLL patients with OPLL (31% vs. 19%; P = 0.049), but there was no difference in incidence of ossification of the ligamentum flavum (13.3% vs. 16.3%; P = 0.546). More OPLL patients preferred a high-salt diet (OPLL/CS, no:somewhat:yes = 23/38:18/25:57/35;, X2 for trend = 6.3; P = 0.001) and pickled foods (OPLL/CS, no:somewhat:yes = 39/56:11/11:48/31; X2 for trend = 6.7; P = 0.0099). Fewer patients with OPLL consumed meat daily (63% vs. 79%; P = 0.018). High-salt diet (odds ratio = 2.62) and daily meat intake (odds ratio = 0.39) showed persistent association with OPLL in a multivariate logistic regression. CONCLUSIONS The similar dietary habits, particularly a high-salt and low meat intakes, may partially explain the high prevalence of OPLL in Taiwan and Japan. Modifying dietary habits may help prevent this disease, especially in those high-risk populations.

Functional Disability Profiles in Amnestic Mild Cognitive Impairment

Background/Aims: Instrumental activities of daily living (IADL) can be impaired in mild cognitive impairment (MCI), and the severity of functional disability predicts Alzheimer’s disease (AD) in amnestic MCI (aMCI). This study investigated the functional profiles of aMCI in a Chinese population. Methods: The Disability Assessment for Dementia scores of 56 subjects with single-domain aMCI (sd-aMCI) and 94 with multiple-domain aMCI (md-aMCI) were compared with normal controls (n = 64) and mild AD patients (n = 102). Results: Both the sd-aMCI (2.5 ± 2.5) and md-aMCI (3.7 ± 3.5) groups had more impaired IADL items than the controls (0.7 ± 1.7). Their IADL scores were intermediate, between the control and AD groups. sd-aMCI subjects presented deficits in 7 IADL items involving the ‘meal preparation’, ‘telephoning’, ‘finance’, ‘medications’, ‘housework’, and ‘leisure’ subscales. md-aMCI subjects presented deficits in 14 IADL items involving all subscales of daily activities. The Mini-Mental State Examination and Modified Trail-Making Test Part B scores were the major neuropsychological correlates of IADL performance in aMCI. Conclusion: IADL can be impaired in both sd-aMCI and md-aMCI. Including the functional ability assessment in the evaluation of aMCI may help clinicians to provide appropriate suggestions to maintain daily functioning.